Comparison of the Efficiency of Dendritic Cell Maturation Upon Stimulation with Bacterial Lipopolysaccharide or Tumor Necrosis Factor Alfa

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E.A. Titov
V.K. Plisova
I.A. Pokusaeva
R.Yu. Saryglar
I.V. Kholodenko
O.A. Bystrykh
A.V. Kuprin
K.N. Yarygin
A.Yu. Lupatov

Abstract

Dendritic cells (DCs) are the professional antigen-presenting cells capable of presenting antigens to T-lymphocytes, thereby initiating the primary immune response. The unique immunological properties of this cell population make their use as a cellular vaccine relevant for the treatment of oncological and chronic infectious diseases. A critical stage in obtaining DCs with immunostimulatory properties is their maturation. To compare the effectiveness of alternative methods for stimulating maturation, DCs were obtained in vitro from peripheral blood monocytes through their induced differentiation in the presence of the cytokines GM-CSF and IL-4. As biochemical stimuli for inducing maturation, bacterial lipopolysaccharide (LPS) or tumor necrosis factor alpha combined with prostaglandin E2 (TNFα+PGE2) were used. No significant differences were found in the ability of these factors to stimulate the expression of HLA-DR and costimulatory molecules (CD80, CD83, CD86). The use of alternative maturations did not lead to differences in the ability of DCs to stimulate the proliferation of allogeneic lymphocytes. At the same time, there were morphological signs indicating the ability of LPS to stimulate differentiation into macrophages.

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How to Cite
Titov, E., Plisova, V., Pokusaeva, I., Saryglar, R., Kholodenko, I., Bystrykh, O., Kuprin, A., Yarygin, K., & Lupatov, A. (2025). Comparison of the Efficiency of Dendritic Cell Maturation Upon Stimulation with Bacterial Lipopolysaccharide or Tumor Necrosis Factor Alfa. Biomedical Chemistry: Research and Methods, 8(4), e00309. https://doi.org/10.18097/BMCRM00309
Section
EXPERIMENTAL RESEARCH

References

  1. Tsapogas, P., Mooney, C. J., Brown, G., Rolink, A. (2017) The cytokine Flt3- ligand in normal and malignant hematopoiesis. Int. J. Mol. Sci., 18(6), 1115. DOI
  2. Segura, E. (2025) Monocyte-derived dendritic cells: an updated view on an old concept. Immunol Rev., 336(1), e70075. DOI
  3. Christopherson, K., Hromas, R. (2001) Chemokine regulation of normal and pathologic immune responses. Stem Cells, 19, 388-396. DOI
  4. Karalkin, P.A., Lupatov, A.Y., Yarygin, K.N. (2009) Endocytosis of microand nanosized particles in vitro by human dendritic cells. Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 3(4), 410-416. DOI
  5. Jarrossay, D., Napolitani, G., Colonna, M., Sallusto, F., Lanzavecchia, A. (2001) Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur. J. Immunol., 31, 3388- 3393. DOI
  6. Figdor, C.G., van Kooyk, Y., Adema, G.J. (2002) C-type lectin receptors on dendritic cells and Langerhans cells. Nat. Rev. Immunol., 2, 77-84. DOI
  7. Masten, B.J., Yates, J.L., Pollard Koga, A.M., Lipscomb, M.F. (1997) Characterization of accessory molecules in murine lung dendritic cell function: roles for CD80, CD86, CD54, and CD40L. Am. J. Respir. Cell. Mol. Biol., 16, 335-342. DOI
  8. Moussion, C., Delamarre, L. (2024) Antigen cross-presentation by dendritic cells: A critical axis in cancer immunotherapy. Semin. Immunol., 71, 101848. DOI
  9. Sander, J., Schmidt, S.V., Cirovic, B., McGovern, N., Papantonopoulou, O., et al. (2017) Cellular differentiation of human monocytes is regulated by timedependent interleukin-4 signaling and the transcriptional regulator NCOR2. Immunity, 47 (6), 1051-1066 DOI
  10. Mahnke, K., Schmitt, E., Bonifaz, L., Enk, A. H., Jonuleit, H. (2002) Immature, but not inactive: the tolerogenic function of immature dendritic cells. Immunol Cell Biol., 80(5), 477-483. DOI
  11. Brigl, M., Brenner, M.B. (2004) CD1: antigen presentation and T cell function. Annu. Rev. Immunol., 22(1), 817-890. DOI
  12. Jonuleit, H., Kuhn, U., Muller, G., Steinbrink, K., Paragnik, L., Schmitt, E., Knop, J., Enk, A.H. (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol., 27, 3135-3142. DOI
  13. Lupatov, A.Yu., Karalkin, P.A., Moldaver, M.V., Burunova, V.V., Poltavtseva, R.A., Gabibullaeva, Z.G., Pavlovich, S.V., Yarygin, K.N., Sukhikh, G.T. (2011) Bone marrow mesenchymal stem cells suppress differentiation of allogeneic dendritic cells in vitro and do not affect their maturation. Immunologiya, 32(3), 122-127.
  14. Winzler, C., Rovere, P., Rescigno, M., Granucci, F., Penna, G., Adorini, L., Zimmermann, V.S, Davoust, J., Ricciardi-Castagnoli, P. (1997) Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures. J. Exp. Med., 185(2) 317-328. DOI
  15. Bourque, J., Hawiger, D. (2023) Life and death of tolerogenic dendritic cells. Trends Immunol., 44(2), 110-118. DOI
  16. Sansom, D.M. (2000) CD28, CTLA-4 and their ligands: who does what and to whom? Immunology, 101(2), 169-177. DOI
  17. Cao, W., Lee, S.H., Lu, J. (2005) CD83 is preformed inside monocytes, macrophages and dendritic cells, but it is only stably expressed on activated dendritic cells. Biochem J., 1, 385(Pt 1), 85-93. DOI
  18. Kawai, T., Akira, S. (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol., 11(5), 373-384. DOI
  19. Horiuchi, T., Mitoma, H., Harashima, S., Tsukamoto, H, Shimoda, T. (2010) Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford), 49(7), 1215-1228. DOI
  20. Akira, S., Uematsu, S., Takeuchi, O. (2006) Pathogen recognition and innate immunity. Cell, 124(4), 783-801. DOI
  21. Sallusto, F., Lanzavecchia, A. (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J. Exp. Med., 179(4), 1109-1118 DOI
  22. Jonuleit, H., Kühn, U., Müller., G., Steinbrink, K., Paragnik L., Schmit, E., Knop, J., Enk, A.H. (1997) Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol., 27(12), 3135-3142. DOI
  23. Lichtenegger, F.S, Mueller, K., Otte, B., Beck, B., Hiddemann, W., Schendel, D.J, Subklewe, M. (2012) CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells. PLoS One, 7(9), e44266. DOI
  24. Dohnal, A.M., Witt, V., Hügel, H., Holter, W., Gadner, H., Felzmann, T. (2007) Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy, 9(8), 755-770. DOI
  25. Boullart, A. C., Aarntzen, E. H., Verdijk, P., Jacobs, J. F., Schuurhuis, D. H., Benitez-Ribas, D., Schreibelt, G., van de Rakt, M. W., Scharenborg, N. M., de Boer, A., Kramer, M., Figdor, C. G., Punt, C. J., Adema, G. J., de Vries, I. J. (2008) Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration. Cancer Immunol Immunother., 57(11), 1589- 1597. DOI